POS0764 IMPACT OF TOFACITINIB TREATMENT ON HEIGHT IN JUVENILE IDIOPATHIC ARTHRITIS
Authors: H. Brunner, H. Wasserman, M. Saul, D. Robinson, E. Nagy, A. Diehl, M. Mortezavi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Diminished growth can be a consequence of juvenile idiopathic arthritis (JIA).<sup>[1]</sup> Growth hormone signals through a Janus kinase (JAK)2 tyrosine kinase-coupled receptor.<sup>[2]</sup> Tofacitinib, an oral JAK inhibitor approved for JIA, preferentially inhibits signalling by heterodimeric receptors associated with JAK1 and/or JAK3 and has less functional selectivity for JAK2. <h3>Objectives</h3> To evaluate the growth of patients (pts) with JIA treated with tofacitinib. <h3>Methods</h3> This post hoc analysis of the Phase 3 trial of tofacitinib in pts with JIA (NCT02592434; a 44-week, 2-part, double-blind [DB], withdrawal study in 225 pts aged 2–&lt;18 years) enrolled 212 pts (pts with systemic JIA were excluded). In part 1, pts received open-label tofacitinib 5 mg twice daily (BID; or weight-based oral solution) for 18 weeks/flare. In the DB phase, pts achieving JIA/American College of Rheumatology improvement ≥30% by Week 18 were randomised to receive tofacitinib or placebo until Week 44/flare. Pts could then receive tofacitinib in a long-term extension study. Height Z-scores were calculated for pts at baseline (BL), Weeks 18, 44, 68 and 92 using age- and sex-matched reference data from the World Health Organization. A repeated measures mixed-effects analysis of pts who received continuous tofacitinib assessed change in height Z-scores over time. The impact of JIA category, age, sex, race, ethnicity, biologic disease-modifying antirheumatic drug (bDMARD)/conventional synthetic DMARD (csDMARD) use, and C-reactive protein (CRP; normal/elevated) on BL height Z-score was also assessed. A separate analysis assessed the impact of treatment on change in height Z-scores during the DB phase. Growth velocity (cm/year) from BL to Week 44 was calculated. <h3>Results</h3> Ethnicity was the only characteristic associated with BL height Z-score (Table 1). For 83 pts who received continuous tofacitinib, mean (95% confidence intervals [CI]) BL height Z-score was -0.4 (-0.7, -0.1), and was stable up to Week 92 (Figure 1). Mean (95% CI) change in height Z-score from BL of the DB phase (Week 18) to Week 44 was not different for pts receiving tofacitinib (N=56; -0.03 [-0.1, 0.04]) vs placebo (N=36; -0.04 [-0.1, 0.04]). Growth velocities in the 56 pts who received tofacitinib for 44 weeks was within normal range for age and sex with peak values at ages 9–10 years and 11–12 years for females and males, respectively (data not shown). <h3>Conclusion</h3> In this post hoc analysis, pts with JIA began with near normal height Z-scores and tofacitinib had no negative impact on height Z-scores after 92 weeks. Growth velocity was within the normal range for age up to Week 44. Catch-up growth was not observed, possibly due to the study duration being too short and the BL height Z-scores being near normal. <h3>References</h3> [1]Gaspari S et al. Clin Exp Rheumatol 2011; 29: 104-10 [2]Carter-Su C et al. Growth Horm IGF Res 2016; 28: 11-5 <h3>Acknowledgements</h3> This study was sponsored by Pfizer. We thank the PRCSG and PRINTO investigators for the collection of serum samples and data used. Medical writing support, under the direction of the authors, was provided by Lauren Hogarth, MSc, CMC Connect, a division of IPG Health Medical Communications, and was funded by Pfizer, New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med 2022;175:1298-1304). <h3>Disclosure of Interests</h3> Hermine Brunner Speakers bureau: Novartis and Pfizer Inc, Consultant of: AbbVie, AstraZeneca/MedImmune, Bayer, Biocon, Boehringer Ingelheim, Bristol Myers Squibb, Cerecor, Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer Inc, Roche, R-Pharm and Sobi, Grant/research support from: Bristol Myers Squibb, Novartis and Pfizer Inc, Employee of: Cincinnati Children's Hospital Medical Center, Halley Wasserman Consultant of: Endocrine Society Pediatric Self-assessment program, NIH-funded trial for skeletal health and bone marrow composition, Grant/research support from: Calcilytix, Ultragenyx, Michelle Saul Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Douglas Robinson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Edward Nagy Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Mahta Mortezavi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.